Hersh: Is hemophilia hereditary?

Q: My little cousin was diagnosed with hemophilia, even though it does not run in our family. How is this possible?

By Dr. Jeff Hersh/Daily News Correspondent

The Enterprise, Brockton, MA

By Dr. Jeff Hersh/Daily News Correspondent

Posted May. 7, 2013 at 12:01 AM
Updated May 7, 2013 at 7:15 AM

By Dr. Jeff Hersh/Daily News Correspondent

Posted May. 7, 2013 at 12:01 AM
Updated May 7, 2013 at 7:15 AM

» Social News

Q: My little cousin was diagnosed with hemophilia, even though it does not run in our family. How is this possible?

A: A cascade of proteins that interact with each other in very specific ways is needed for normal blood clotting, which is what stops bleeding. Hemophilia is a condition where there is an insufficient amount of one of these proteins, hence hemophiliacs have abnormal bleeding.

About 85 percent of hemophilia is type A, due to insufficient amounts of factor VIII; hemophilia B (also called Christmas disease and due to insufficient factor IX) accounts for almost 15 percent of cases. The genes for factors VIII and IX are on the x chromosome (one of the sex determining chromosomes), and are inherited in a recessive manner (meaning with even one normal gene the patient will not manifest the disease).

Women have two x chromosomes, so they do not typically develop hemophilia A or B (there are some uncommon scenarios where a woman will have symptomatology). Men have one x and one y chromosome, so if their x chromosome is abnormal they will manifest symptoms. From this it is evident that all female children of a man with hemophilia will be carriers, but a son cannot inherit this condition from his father since to be a boy he must get his y chromosome from his father and the disease is carried on the x chromosome.

A third type of hemophilia, type C, is due to insufficient amounts of factor XI; it is dominantly inherited (only one affected gene causes symptoms so it can occur in females as well as males) and is rare.

About one in 5,000 male babies are born with hemophilia. Most cases are suspected due to a positive family history of the disease and may then be verified by testing. However, about 30 percent of cases are not inherited; instead they are thought to be due to a spontaneous gene mutation.

The severity of hemophilia symptoms depend on the level of the clotting factor. Non-affected people have levels anywhere between 50 to 150 percent of "normal" (with 100 percent being the average for an unaffected person). Patients with mild hemophilia have over five percent of normal amounts, moderates have one to five percent and severe hemophiliacs have less than one percent of normal levels.

Patients with mild disease usually only have excessive bleeding in response to trauma or surgery. Although mild disease may be diagnosed early in life (for example due to excess bleeding after circumcision), many of these patients do not have symptoms early in life and in the absence of screening (because of no family history) may not be diagnosed until adolescence or later.

Patients with moderate disease may have excess bleeding as a complication of injuries or certain diseases. This level of hemophilia does not usually manifest until the child starts to walk, when injuries become more common.

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Patients with severe hemophilia may have spontaneous bleeding episodes. Some of these patients will develop symptoms at or shortly after birth, especially if there is trauma during the birthing process. Some will have episodes of bleeding throughout their lives, which may include bleeding into the brain and/or (especially after the child starts to ambulate) into the joints or the muscles. Spontaneous bleeding in the gastrointestinal or genitourinary tracts may also occur.

Hemophilia can be diagnosed by blood tests, which demonstrate problems with blood clotting and when indicated, low levels of the specific blood clotting factors. This testing may be indicated in boys born to a mother with a family history of hemophilia or may be ordered due to suspicion because of abnormal bleeding.

Bleeding episodes in hemophiliacs are treated with replacement of the deficient clotting factor, obtained either from donated blood or produced using recombinant DNA techniques. Certain other medications may be used as well. Minimizing bleeding episodes, for example by avoiding traumatic injuries, is important as well. Patients with severe disease that have frequent bleeding episodes may be prophylactically treated with clotting factor infusions.

Hemophiliacs who have frequent bleeding into their joints may develop joint deformities, and those requiring frequent clotting factor treatments can develop antibody responses to these factors, making them less beneficial and causing other problems. Other complications may occur as well.

Hemophiliacs should be followed by a specialist and should consider being treated at a hemophilia treatment center. Research in gene therapy shows promise of developing treatments that may allow hemophiliacs to produce normal clotting factor levels on their own, and other treatment strategies are also being investigated that will hopefully improve the lives of patients affected by this condition.